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We prove the global space-time bound for the defocusing mass critical nonlinear Schrödinger equation on R 3 perturbed by a small multiplicative noise. The associated scattering behavior is also obtained. In addition to techniques from Fan and Xu (Global well-posedness for the defocusing mass-critical stochastic nonlinear Schrödinger equation on R at L 2 regularity, 2018) and Fan and Zhao (On long time behavior for stochastic nonlinear Schrödinger equations with a multiplicative noise, 2020), the main new ingredients are the decomposition of the solution tailored for the bootstrap argument in this problem, and the incorporation of local smoothing norms to close the argument. We also prove the global space-time Strichartz estimate for the linear stochastic equation. It is a toy model of our nonlinear problem, but the bound itself is new and of its own interest. Furthermore, the proof we give for the linear model is more direct, and also illustrates the proof strategy for the nonlinear problem. [ABSTRACT FROM AUTHOR]

Coronavirus 2019 (COVID‐19) has caused violent fluctuation in stock markets, and led to heated discussion in stock forums. The rise and fall of any specific stock is influenced by many other stocks and emotions expressed in forum discussions. Considering the transmission effect of emotions, we propose a new Textual Multiple Auto Regressive Moving Average (TM‐ARMA) model to study the impact of COVID‐19 on the Chinese stock market. The TM‐ARMA model contains a new cross‐textual term and a new cross‐auto regressive (AR) term that measure the cross impacts of textual emotions and price fluctuations, respectively, and the adjacent matrix which measures the relationships among stocks is updated dynamically. We compute the textual sentiment scores by an emotion dictionary‐based method, and estimate the parameter matrices by a maximum likelihood method. Our dataset includes the textual posts from the Eastmoney Stock Forum and the price data for the constituent stocks of the FTSE China A50 Index. We conduct a sliding‐window online forecast approach to simulate the real‐trading situations. The results show that TM‐ARMA performs very well even after the attack of COVID‐19. [ABSTRACT FROM AUTHOR]

[Display omitted] Hydrogel-based drug delivery holds great promise in topical tumor treatment. However, the simple construction of multifunctional therapeutic hydrogels under physiological conditions is still a huge challenge. Herein, for the first time, a multifunctional hyaluronan/MnO 2 nanocomposite (HHM) hydrogel with injectable and self-healing capabilities was constructed under physiological conditions through innovative in situ mineralization-triggered Mn-hydrazide coordination crosslinking. The hydrogel formed from Mn2+ and hydrazided hyaluronan under optimized conditions exhibited a high elastic modulus >1 kPa, injectability, self-healing function, stimuli-responsiveness and catalase-like activity. In vitro and in vivo biological experiments demonstrated that our HHM hydrogel could not only efficiently relieve hypoxia by in situ catalytic decomposition of endogenous H 2 O 2 into O 2 but also achieve synergistic photodynamic/photothermal therapy of 4T1 breast cancer in a mouse tumor model. This study presented a novel mineralization-driven metal-hydrazide coordination crosslinking approach and developed a multifunctional therapeutic platform for O 2 -enhanced efficient topical dual-phototherapy of breast cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] Hydrogel-based drug delivery holds great promise in topical tumor treatment. However, the simple construction of multifunctional therapeutic hydrogels under physiological conditions is still a huge challenge. Herein, for the first time, a multifunctional hyaluronan/MnO 2 nanocomposite (HHM) hydrogel with injectable and self-healing capabilities was constructed under physiological conditions through innovative in situ mineralization-triggered Mn-hydrazide coordination crosslinking. The hydrogel formed from Mn2+ and hydrazided hyaluronan under optimized conditions exhibited a high elastic modulus >1 kPa, injectability, self-healing function, stimuli-responsiveness and catalase-like activity. In vitro and in vivo biological experiments demonstrated that our HHM hydrogel could not only efficiently relieve hypoxia by in situ catalytic decomposition of endogenous H 2 O 2 into O 2 but also achieve synergistic photodynamic/photothermal therapy of 4T1 breast cancer in a mouse tumor model. This study presented a novel mineralization-driven metal-hydrazide coordination crosslinking approach and developed a multifunctional therapeutic platform for O 2 -enhanced efficient topical dual-phototherapy of breast cancer. [ABSTRACT FROM AUTHOR]

Cuproptosis is a very newly recognized regulated cell death modality that is distinct from known death mechanisms and shows enormous prospect in cancer treatment. However, its efficacy is copper‐dependent and restricted by strictly regulated copper metabolism. Herein, a novel copper/iron hybrid hollow amorphous metal organic framework (HaMOF) is developed as an oxidative stress amplifier and copper/iron metabolic disrupter for synergistic cuproptosis/ferroptosis/apoptosis anticancer therapy. The HaMOF is fabricated from Cu2+, 3,3′‐dithiobis(propionohydrazide) and Fe3+ via an unsaturated coordination‐etching integration strategy, and then doxorubicin is loaded followed by surface decoration with hyaluronan. The obtained DOX@Fe/CuTH exhibits tumor microenvironment‐triggered catalytic therapeutic property, wherein it can amplify cellular oxidative stress by simultaneously boosting H2O2 production and depleting glutathione. Moreover, it can cause mitochondrial dysfunction and downregulate the expressions of copper transporter ATP7A and iron transporter FPN 1, thereby leading to metabolic disorders and high retentions of copper/iron in cytoplasm for •OH generation. The overloaded Cu2+ can cause lipoylated protein dihydrolipoamide S‐acetyltransferase aggregation and lead to cellular cuproptosis. Collectively, both augmented oxidative stress and overloaded copper/iron induce potent ferroptosis, which synergizes with cuproptosis and DOX‐mediated apoptosis to efficiently suppress tumor growth. This bimetallic hollow nanoplatform provides a new therapeutic modality paradigm to boost cuproptosis‐related therapies. [ABSTRACT FROM AUTHOR]

The reduction of selenite [Se(Ⅳ)] by microorganisms is a green and efficient detoxification strategy. We found that Se(Ⅳ) inhibited exopolysaccharide and protein secretion by Lactiplantibacillus plantarum BSe and compromised cell integrity. In this study, L. plantarum BSe reduced Se(Ⅳ) by increasing related enzyme activity and electron transfer. Genomic analysis demonstrated that L. plantarum BSe should be able to reduce Se(Ⅳ). Further transcriptome analysis showed that L. plantarum BSe enhanced its tolerance to Se(Ⅳ) by upregulating the expression of surface proteins and transporters, thus reducing the extracellular Se(Ⅳ) concentration through related enzymatic reactions and siderophore-mediated pathways. Lactiplantibacillus plantarum BSe was able to regulate the expression of related genes involved in quorum sensing and a two-component system and then select appropriate strategies for Se(Ⅳ) transformation in response to varying environmental Se(Ⅳ) concentrations. In addition, azo reductase was linked to the reduction of Se(Ⅳ) for the first time. The present study established a multipath model for the reduction of Se(Ⅳ) by L. plantarum , providing new insights into the biological reduction of Se(Ⅳ) and the biogeochemical cycle of selenium. [Display omitted] • Se(Ⅳ) compromised cell integrity of L. plantarum BSe and inhibited EPS secretion. • BSe reduces Se(Ⅳ) by improving enzyme activity and electron transfer. • BSe upregulated surface proteins and transporters to resist the Se(Ⅳ) stress. • Azo reductase was found to be related to the reduction of Se(Ⅳ) for the first time. [ABSTRACT FROM AUTHOR]

In group decision making, it is sensible to achive minimum consensus cost (MCC) because the consensus reaching process resources are often limited. In this endeavour, though, there are still two issues that require paying attention to: (1) the impact of decision rules, including decision weights and aggregation functions, on MCC; and (2) the impact of non-cooperative behaviors on MCC. Hence, this paper analytically reveals the decision rules to minimize MCC or maximize MCC. Furthermore, detailed simulation experiments show the joint impact of non-cooperative behavior and decisions rules on MCC, as well as revealing the effect of the consensus within the established MCC target. [ABSTRACT FROM AUTHOR]

Studies have demonstrated that both mortality and severe illness rates exist significant difference in different gender COVID-19 patients, but the reasons are still very mysterious to date. Here, we firstly find that the survival outcome of female patients is better to male patients through analyzing the 3044 COVID-19 cases. Secondly, we identify many important master regulators [e.g. STAT1/STAT2 and zinc finger (ZNF) proteins], in particular female patients can express more ZNF proteins and stronger transcriptional activities than male patients in response to SARS-CoV-2 infection. Thirdly, we discover that ZNF protein activity is significantly negative correlation with the SARS-CoV-2 load of COVID-19 patients, and ZNF proteins as transcription factors can also activate their target genes to participate in anti-SARS-CoV-2 infection. Fourthly, we demonstrate that ZNF protein activity is positive correlation with the abundance of multiple immune cells of COVID-19 patients, implying that the highly ZNF protein activity might promote the abundance and the antiviral activity of multiple immune cells to effectively suppress SARS-CoV-2 infection. Taken together, our study proposes an underlying anti-SARS-COV-2 role of ZNF proteins, and differences in the amount and activity of ZNF proteins might be responsible for the distinct prognosis of different gender COVID-19 patients. [ABSTRACT FROM AUTHOR]

Under the Gaussian noise assumption, the probability hypothesis density (PHD) filter represents a promising tool for tracking a group of moving targets with a time-varying number. However, inaccurate prior statistics of the random noise will degrade the performance of the PHD filter in many practical applications. This paper presents an adaptive Gaussian mixture PHD (AGM-PHD) filter for the multi-target tracking (MTT) problem in the scenario where both the mean and covariance of measurement noise sequences are unknown. The conventional PHD filters are extended to jointly estimate both the multi-target state and the aforementioned measurement noise statistics. In particular, the Normal-inverse-Wishart and Gaussian distributions are first integrated to represent the joint posterior intensity by transforming the measurement model into a new formulation. Then, the updating rule for the hyperparameters of the model is derived in closed form based on variational Bayesian (VB) approximation and Bayesian conjugate prior heuristics. Finally, the dynamic system state and the noise statistics are updated sequentially in an iterative manner. Simulations results with both constant velocity and constant turn model demonstrate that the AGM-PHD filter achieves comparable performance as the ideal PHD filter with true measurement noise statistics. [ABSTRACT FROM AUTHOR]

Mean reversion is an important property when constructing efficient contrarian strategies. Researchers observe that mean reversion has multiperiodical and asymmetric nature simultaneously in real market. To better utilize mean reversion and improve the existing online portfolio selection strategies, we propose a new online strategy named multiperiodical asymmetric mean reversion (MAMR). The MAMR strategy incorporates a multipiecewise loss function with the moving average method and then imitates the passive-aggressive algorithm. We further provide a solution via convex optimization. This strategy runs in linear time and thus is suitable for large-scale trading applications. Our empirical results testing six real market datasets show that this strategy can achieve better results in bearing higher transaction cost. [ABSTRACT FROM AUTHOR]

We show robustness of various truncated and subcritical approximations to the stochastic defocusing mass-critical nonlinear Schrödinger equation (NLS) in dimension d = 1 , whose solution was constructed in [8] with one particular such approximation. The key ingredient in the proof is a uniform bound of the solutions to the family of deterministic mass-subcritical defocusing NLS. [ABSTRACT FROM AUTHOR]

5‐(2‐Oxopropylideneamino)‐6‐d‐ribitylaminouracil (5‐OP‐RU) is a natural product formed during bacterial synthesis of vitamin B2. It potently activates mucosal associated invariant T (MAIT) cells and has immunomodulatory, inflammatory, and anticancer properties. This highly polar and unstable compound forms a remarkably stable Schiff base with a lysine residue in major histocompatibility complex class I–related protein (MR1) expressed in antigen‐presenting cells. Inspired by the importance of the ribityl moiety of 5‐OP‐RU for binding to both MR1 and the T cell receptor (TCR) on MAIT cells, each OH was removed in silico. DFT calculations and MD simulations revealed a very stable hydrogen bond between the C3′−OH and uracil N1H, which profoundly restricts flexibility and positioning of each ribityl‐OH, potentially impacting their interactions with MR1 and TCR. By using deoxygenation strategies and kinetically controlled imine formation, four monodeoxyribityl and four monohydroxyalkyl analogues of 5‐OP‐RU were synthesised as new tools for probing T cell activation mechanisms. [ABSTRACT FROM AUTHOR]

Brassinosteroids (BRs) are essential hormones for plant growth and development. Enzymes DET2 and CYP90 family are responsible for BR biosynthesis in seed plants. Yet, their roles in non-seed plants are unknown. Here, we report the first functional study of DET2 and all 4 CYP90 genes isolated from Selaginella moellendorfii. Sm89026 (SmCPD) belonged to a clade with CYP90A1 (CPD) and CYP90B1 (DWF4) while Sm182839, Sm233379 and Sm157387 formed a distinct clade with CYP90C1 (ROT3) and CYP90D1. SmDET2, SmCPD and Sm157387 were highly expressed in both leaves and strobili while Sm233379 was only highly expressed in the leaves but not strobili, implying their differential functions in a tissue-specific manner in S. moellendorfii. We showed that only SmDET2 and SmCPD completely rescued Arabidopsis det2 and cpd mutant phenotypes, respectively, suggestive of their conserved BR biosynthetic functions. However, neither SmCPD nor other CYP90 genes rescued any other cyp90 mutants. Yet overexpression of Sm233379 altered plant fertility and BR response, which means that Sm233379 is not an ortholog of any CYP90 genes in Arabidopsis but appears to have a BR function in the S. moellendorfii leaves. This function is likely turned off during the development of the strobili. Our results suggest a dramatic functional divergence of CYP90 family in the non-seed plants. While some of them are functionally similar to that of seed plants, the others may be functionally distinct from that of seed plants, shedding light for future exploration. [ABSTRACT FROM AUTHOR]

The two-slope online leasing problem is a natural generalization of the classic online leasing problem. Due to the fact that the two-slope online leasing problem of continuous-time has already been studied, we focus on the two-slope online leasing problem of discrete time in this study. Our discussion has taken the deterministic strategy and the randomized strategy into consideration. We demonstrated an optimal deterministic strategy, which could achieve competitive factor of 2 - [1 + (s - 1)a]/s. As for the randomized strategy, we proposed the strategy of risk balanced its absolute optimality through competitive analysis. Finally, analysis and discussions are carried out for the two types of strategies, mainly based on their competitive performances. It is found that, the two-slope analysis could improve the competitive ratio of the classic online leasing problems. In addition, by taking the discreteness into consideration rather than the continuity, the effectiveness of solving online leasing problem could be much improved. [ABSTRACT FROM AUTHOR]

Highlights • HA hydrogel was prepared via hydrazone-/photo- dual crosslinking process. • HA hydrogel had topography and mechanical property similar to breast tumor tissue. • HA hydrogel promoted MCF-7 cells to cluster and secrete VEGF, bFGF and IL-8. • 3D culture enhanced cell migration and invasion potentials and in vivo tumorigenesis. Abstract In tumor biology, it is widely recognized that 3D rather than 2D cell culture can recapitulate key features of solid tumors, including cell-extracellular matrix (ECM) interactions. In this study, to mimick the ECM of breast cancer, hyaluronic acid (HA) hydrogels were synthesized from two polyvalent HA derivatives through a hydrazone and photo dual crosslinking process. HA hydrogels could be formed within 120 s. The hydrogels had similar topography and mechanical properties to breast tumor and displayed glutathione and hyaluronidase dual-responsive degradation behavior. Biological studies demonstrated that HA hydrogel could support the proliferation and clustering of breast cancer MCF-7 cells. The expression levels of VEGF, IL-8 and bFGF in hydrogel-cultured cells were significantly greater than those in 2D culture. Moreover, cells from hydrogel culture exhibited greater migration/invasion abilities and tumorigenicity than 2D-cultured cells. Therefore, the HA hydrogels are a promising ECM-mimicking matrix for in vitro construction of breast cancer. [ABSTRACT FROM AUTHOR]

Abstract The food sector produces large amounts of greenhouse gas (GHG) emissions, which has attracted attention of many researchers. Previous studies evaluated food carbon footprints (CFs) mainly based on food weight. Nutrient content of food could reflect food function better. However, different conclusions could be drawn based on different individual nutrients. The comprehensive trophic index has been used to evaluate food nutrition. In this study, CFs of nineteen carbohydrate-rich (CR) foods including grains, beans, root and tuber-food were investigated based on different functional units (weight, energy, protein, carbohydrate, and two comprehensive trophic indexes Nu 21 and Nu 11). The CF rankings of the foods varied when weight based-, energy based-, and individual nutrient based functional units were used. Potato, cereal foods, and beans showed the low-CF advantage when weight based-, carbohydrate based-, and protein based functional unit was used, respectively. Covering more nutrients in the functional unit is beneficial to get closer to the truth of environmental impact of different foods. The comprehensive trophic index based functional unit was more appropriate for illustrating food CFs. Nu 21 method was fairer to evaluate food CF from the viewpoint of individual food, while Nu 11 method was more appropriate from the viewpoint of balanced diet. The results also exhibited that consumption of more brown rice and standard grade flour could be a feasible plan to reduce carbon emissions in nowadays. Meanwhile, enhancing rotation of coarse cereals and increasing consumption of coarse foods could cut a considerable amount of carbon emissions further. Highlights • CFs of nineteen CR foods were investigated according to the LCA principle. • CFs of foods were evaluated based on different functional units. • Comprehensive evaluation of nutritional function was important to evaluate food CF. • Two nutrition profiling models were more appropriate to evaluate food CF. [ABSTRACT FROM AUTHOR]

In this note, we use the Feynman–Kac formula to derive a moment representation for the 2D parabolic Anderson model in small time, which is related to the intersection local time of planar Brownian motions. [ABSTRACT FROM AUTHOR]

The aim of this paper is pricing the vulnerable options in a vague world. Due to the vulnerability of financial markets and the economy environment in the real world, investors cannot always have precise information about firm value and default recovery rate in vulnerable option pricing. Therefore, following the framework of Klein in 1996, a fuzzy binomial tree pricing model is derived by modelling the firm value and default recovery rate as fuzzy numbers. The numerical results show that the precise information assumption about the firm value and recovery rate in Klein model may lead to underestimate the credit risk on the values of vulnerable options. This study aims to provide insights for future research on defaultable options pricing under imprecise market information. [ABSTRACT FROM AUTHOR]

Load carrying capacity is of importance in the evaluation of the stability of submarine pressure shell structure. During the buckling process of cylindrical shell under hydrostatic pressure, the total potential energy of ring-stiffened cylindrical shell can be divided into constant component, linear component and square nonlinear component. Based on the derivations of buckling loads of smooth cylindrical shell and ring-stiffened cylindrical shell, the reduced stiffness method (RSM) is applied to assess the role of different stiffness reductions in the evaluation of stable load carrying capacity of cylindrical shell. This study shows: (1) the circumferential membrane stiffness is influence the stability of cylindrical shell largest; (2) the ring ribs have a significant effect on the overall stability of ring-stiffened cylindrical shells under hydrostatic pressure; (3) the circumferential buckling wave number of ring-stiffened cylindrical shell may not depend on the membrane stiffness reduction of shell, but it increases with the bending stiffness reduction of ring ribs. [ABSTRACT FROM AUTHOR]

The FastSLAM relies on particles sampled from the proposal distribution of underlying Rao–Blackwellized particle filter, and its performance is significantly influenced by the quality and quantity of the particles. In this paper, a new improved FastSLAM is proposed based on transformed unscented Kalman filter (TUKF) and Kullback–Leibler distance (KLD) resampling method. In the proposed algorithm, a square-root extension of TUKF is used to calculate the proposal distribution and to generate credible particles. In addition, during the resampling process, the minimum required number of particles is determined adaptively by bounding the KLD error between the sample-based approximation and true posterior distribution of the robot state. Both numerical simulations and real-world dataset experiments are used to evaluate the performance of the proposed algorithm. The results indicate that the proposed algorithm achieves higher estimation accuracy and computational efficiency than conventional approaches. [ABSTRACT FROM AUTHOR]

We develop a simple procedure that allows one to explicitly reconstruct any piecewise linear path from its signature. The construction is based on the development of the path onto the hyperbolic space. [ABSTRACT FROM AUTHOR]

This work includes the design of fully flexible wearable data glove to ensure that strain sensors are accurately connected to the hand joints to accurately measure the joints motions of the finger joints. A real-time flexible wearable gesture-to-alphabets translation system was reported of integrating visual data with somatosensory data from ten flexible stretchable sensors-based data glove and a camera, assisted by machine learning. The device recognized the 26 letters with a recognition rate of up to 99.63% and a recognition time of less than 1 s, which helps to understand observations of sign as words and texts. [Display omitted] • The design of fully flexible wearable data glove. • A system of sign annotation generation to words via integrating visual data with somatosensory data from flexible strain sensor-based data glove is constructed, and the effectiveness of the proposed system is demonstrated through experiments for quantitative evaluations. • A real-time flexible wearable gesture-to-alphabets translation system was reported. • The device recognized the 26 letters with a recognition rate of up to 99.63% and a recognition time of <1 s. Sign language forms a significant way of communication for deaf-mute people. There are different types of sign languages of different countries in different regions. The sign language recognition system translates the gestures into the alphabet, which solves a barrier in comprehension of conversation. Visual techniques and somatosensory strain sensors are both useful modalities to detect sign gesture. In order to improve the recognition accuracy and wear resistance, this paper proposes a real-time alphabets conversion system, which combines the visual data with the data glove based on flexible strain sensor and the somatosensory data of the camera, supplemented by deep learning. In this learning structure, convolutional neural network is used to process the visual data, and then the sparse neural network for sensor data fusion and recognition is realized in the feature layer. A module is proposed to train the linking of hand motions primitives to alphabets (A–Z). The proposed framework is tested on a dataset of sign and descriptive alphabets. The proposed system would recognize the 26 letters with a recognition rate of up to 99.50% and a recognition time of less than 1 s, which helps to understand observations of sign as words and texts. [ABSTRACT FROM AUTHOR]

Prostate cancer gene expression marker 1 (PCGEM1) has been identified as an oncogenic long non-coding RNA (lncRNA) in diverse cancers, but it has never been linked with colorectal cancer (CRC). Former studies have shown the mutual regulation between lncRNAs and transcription factors (TFs) in cancer. CCCTC binding factor (CTCF) has been reported to transcriptionally activate lncRNAs in cancers. We predicted the binding of CTCF on PCGEM1 promoter through UCSC (https://genome.ucsc.edu/), but their relation has not been studied. We aimed to investigate whether and how PCGEM1 functioned in CRC cells and the interaction between PCGEM1 and CTCF. The impacts of PCGEM1 and CTCF inhibition on CRC cells were verified through loss-of-function experiments. Mechanism experiments were used to prove the binding between CTCF and PCGEM1 in CRC progression. PCGEM1 possessed a high expression level in CRC cells as well as tumors. CTCF transcriptionally activated PCGEM1 expression. Knockdown of PCGEM1 or CTCF impeded proliferation and migration and drove apoptosis of CRC cells. Moreover, PCGEM1 bound miR-433–3p to prevent miR-433–3p from targeting CTCF. We first revealed PCGEM1/miR-433–3p/CTCF positive feedback loop as an oncogenic axis in CRC cells, which potentially provides new clues for the advancement of CRC treatment. [ABSTRACT FROM AUTHOR]

• A pioneering "grafting from" drug coordination polymerization strategy was proposed. • A fully-coordinated and full-active Cu 2 O/drug core/shell nanoplatform was prepared. • Obtained nanoplatform-mediated ROS storm could induce immunogenic cell death. • Nanoplatform/αPD-1 combination could induce robust systemic antitumor immunity. Precise manipulation of reactive oxygen species (ROS) breakthrough threshold exhibits great potential in destroying solid tumors, reprogramming "immune-cold" tumor and potentiating immunotherapy. However, it is still challenging to develop efficient ROS initiation devices. Herein, we propose a pioneering "grafting from" drug coordination polymerization strategy and develop a fully-coordinated and full-active Cu 2 O/drug core/shell nanoparticles for multimodal cancer therapy. Chemotherapeutic drug cisplatin (CDDP) and photosensitizer indocyanine green (ICG) were loaded onto the surface of hydrazided hyaluronic acid-decorated Cu 2 O (HA-Cu 2 O) nanoparticles through an infinite hydrazide-cisplatin-sulfonic acid coordination mechanism, obtaining CDDP/ICG-coloaded HA-Cu 2 O (HCCI) nanoplatform. The HCCI nanoplatform exhibited a rapid acid-responsive dissociation behavior and released ICG, Cu+ and CDDP to achieve efficient triple combined photodynamic therapy/chemodynamic therapy/chemotherapy. Importantly, such a combination induced efficient immunogenic cell death cascade mediated by powerful ROS storm to reprogram "immune-cold" tumors and potentiate immunotherapy. The combination of HCCI nanoplatform and αPD-1 not only eradicated primary tumors but effectively inhibited distal tumor growth, lung metastasis and tumor recurrence through reprogramming tumor microenvironment and activating CD8+ T cell antitumor immunity. Collectively, we have presented a drug coordination polymerization loading strategy to develop a robust multimodal antitumor nanoplatform, and this study provides a new direction for the design of nanodrug delivery systems. [ABSTRACT FROM AUTHOR]

The aim of this paper is to quantitatively evaluate the extent of collapse of a bulk carrier when the ship is subjected to extreme wave loads. A hydro-elastoplasticity theory, which was proposed by the present authors and takes into account the interaction between the large elasto-plastic deformation and the wave load evaluation, is applied to the ship’s structure with the assumption that a plastic hinge is formed in the midship region when the hull girder collapses in extreme wave conditions. The dynamic response of the hinge can be expressed by the relationship between the vertical bending moment and the curvature, which are obtained using nonlinear Finite Element Analysis (FEA). A comparative correct moment–curvature curve and a reasonable load evaluation are necessary for prediction of the severity of the collapse for the actual ship. A bulk carrier hull model with one frame space is constructed and analysed using an arc-length control method (Riks method). The geometric nonlinearity resulting from large deformations and the material nonlinearity are taken into account. The presence of an initial imperfection is considered using the consistent imperfection mode method in the FEA. A prediction of the extent of collapse for a bulk carrier subjected to an extreme wave load is carried out using the hydro-elastoplasticity approach. This analysis clarifies the extent to which the hull girder may collapse in extreme wave conditions at an exceedance probability of 1/1000 in several short-term sea states. [ABSTRACT FROM AUTHOR]

Abstract: We study a class of three‐dimensional continuous phase coexistence models, and show that, under different symmetry assumptions on the potential, the large‐scale behavior of such models near a bifurcation point is described by the dynamical Φ 3 p models for p ∊ {2,3,4}. This result is specific to space dimension 3 and does not hold in dimension 2. © 2018 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A novel and all-active aMOF, DOX@FeTH, is developed via a one-step self-assembly strategy. The aMOF can effectively suppress tumor growth via a ferroptosis-apoptosis synergetic therapeutic modality. Moreover, the aMOF has excellent photothermal performance and the hyperthermia can enhance tumor penetration and further improve antitumor effect. Owing to simple ingredients, facile preparation process, and integrated multifunctionalities, DOX@FeTH aMOF holds great potential for clinical translation. [Display omitted] • A novel aMOF with triple-stimuli responsiveness was prepared via one-pot method. • The aMOF with favorable photothermal effect could penetrate deeply into tumor. • Self-supplied Fe2+, inactivated GPX4 and elevated H 2 O 2 co-induced ferroptosis. • The aMOF killed tumor cells via a ferroptosis-apoptosis synergistic modality. The combination of ferroptosis and apoptosis that act with different mechanisms holds enormous potential in cancer treatment. However, how to simply but effectively integrate the two modalities into a single platform is an enormous challenge. Herein, based on our newly discovered Fe(II)-hydrazide coordination self-assembly strategy, we design and develop an all-active amorphous metal organic framework (aMOF) for photothermally boosted ferroptosis-apoptosis synergistic anti-tumor therapy. The aMOF is prepared via one-pot co-assembly of doxorubicin (DOX), Fe2+ ions and 3,3′-dithiobis(propionohydrazide) (TPH) and subsequent decoration with TPH-functionalized hyaluronic acid. The obtained DOX@FeTH is amorphous in structure, and it exhibits favorable photothermal performance and displays pH/GSH/laser triple-responsive degradation behavior. The aMOF can be specifically internalized by CD44-overexpressed 4T1 cells and efficiently inhibit GPX4 activity via disulfide bond-mediated glutathione depletion, elevate intracellular H 2 O 2 level by DOX-induced NOX4 activation, and consequently amplify lipid peroxidation with the assistance of self-supplied Fe2+, resulting in remarkable ferroptotic cell death. Meanwhile, the released DOX causes apoptotic cell death. Moreover, the aMOF-mediated hyperthermia can promote tumor penetration and augment the synergistic efficacy. Hence, the tumors are effectively suppressed by the synergistic treatment of DOX@FeTH with laser. This work provides a new strategy for fabricating aMOFs and opens a new horizon for tumor treatment. [ABSTRACT FROM AUTHOR]

Accurately predicting relative binding affinities and biological potencies for ligands that interact with proteins remains a significant challenge for computational chemists. Most evaluations of docking and scoring algorithms have focused on enhancing ligand affinity for a protein by optimizing docking poses and enrichment factors during virtual screening. However, there is still relatively limited information on the accuracy of commercially available docking and scoring software programs for correctly predicting binding affinities and biological activities of structurally related inhibitors of different enzyme classes. Presented here is a comparative evaluation of eight molecular docking programs (Autodock Vina, Fitted, FlexX, Fred, Glide, GOLD, LibDock, MolDock) using sixteen docking and scoring functions to predict the rank-order activity of different ligand series for six pharmacologically important protein and enzyme targets (Factor Xa, Cdk2 kinase, Aurora A kinase, COX-2, pla2g2a, β Estrogen receptor). Use of Fitted gave an excellent correlation (Pearson 0.86, Spearman 0.91) between predicted and experimental binding only for Cdk2 kinase inhibitors. FlexX and GOLDScore produced good correlations (Pearson > 0.6) for hydrophilic targets such as Factor Xa, Cdk2 kinase and Aurora A kinase. By contrast, pla2g2a and COX-2 emerged as difficult targets for scoring functions to predict ligand activities. Although possessing a high hydrophobicity in its binding site, β Estrogen receptor produced reasonable correlations using LibDock (Pearson 0.75, Spearman 0.68). These findings can assist medicinal chemists to better match scoring functions with ligand-target systems for hit-to-lead optimization using computer-aided drug design approaches. [ABSTRACT FROM AUTHOR]

A modified internal circulation (MIC) reactor with an external circulation system was proposed and the performance of treating dyeing wastewater using both MIC and typical IC reactor were compared. Utilization of the external circulation system in the MIC reactor could dramatically improve the mixing intensity of the biomass with the wastewater and resulted in better performance. The COD removal efficiency, biogas production, volatile fatty acids and effluent color were approximately 87%, 98 L d −1 , 180 mg L −1 and 100 times, respectively, in the MIC reactor with a hydraulic retention time of 5 h and organic loading rate of 15 kg COD m −3 d −1 . The hydrodynamics of the MIC reactor under different flows rate of external circulation were also analyzed using computational fluid dynamics (CFD) method. The optimal flow rate of external circulation was 12 L min −1 , which resulted in a corresponding up-flow velocity of 40 m h −1 . The consistency of the result between experiment and simulation validated the scientificity of CFD technique applied to numerical simulation of the MIC reactor. [ABSTRACT FROM AUTHOR]

Abstract: In this study, poly(l-lactide-co-β-malic acid) (PLMA) copolymer was synthesized via ring-opening polymerization of l-lactide and β-benzyloxycarbonyl-β-propiolactone, followed by removal of benzyl protective groups through hydrogenolysis. Novel biomorphic PLMA scaffolds with a honeycomb-like structure were prepared using cane as template. We investigated the chemical structure and physicochemical properties of PLMA copolymer and the morphology and biocompatibility of biomorphic PLMA scaffolds. The results confirmed the chemical structure of PLMA copolymer. The amorphous copolymer had a glass transition temperature of 49°C. The PLMA scaffolds well retained the morphology of cane, and had a porosity of 85.5% and a compressive modulus of 766.2±36.1kPa. in vitro biocompatibility evaluation with MC3T3-E1 cells demonstrated the potential of the biomorphic PLMA scaffolds for bone tissue engineering. [Copyright &y& Elsevier]

In this study, biomorphic poly(dl-lactic-co-glycolic acid)/nano-hydroxyapatite (PLGA/nHA) composite scaffolds were successfully prepared using cane as a template. The porous morphology, phase, compression characteristics and in vitro biocompatibility of the PLGA/nHA composite scaffolds and biomorphic PLGA scaffolds as control were investigated. The results showed that the biomorphic scaffolds preserved the original honeycomb-like architecture of cane and exhibited a bimodal porous structure. The average channel diameter and micropore size of the PLGA/nHA composite scaffolds were 164±52μm and 13±8μm, respectively, with a porosity of 89.3±1.4%. The incorporation of nHA into PLGA decreased the degree of crystallinity of PLGA, and significantly improved the compressive modulus of biomorphic scaffolds. The in vitro biocompatibility evaluation with MC3T3-E1 cells demonstrated that the biomorphic PLGA/nHA composite scaffolds could better support cell attachment, proliferation and differentiation than the biomorphic PLGA scaffolds. The localization depth of MC3T3-E1 cells within the channels of the biomorphic PLGA/nHA composite scaffolds could reach approximately 400μm. The results suggested that the biomorphic PLGA/nHA composite scaffolds were promising candidates for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract: It is well known that for two p-rough paths, if their first levels of iterated integrals are close in p-variation sense, then all levels of their iterated integrals are close. In this paper, we prove that a similar result holds for the paths provided the first terms are close in a ‘uniform’ sense. The estimate is explicit, dimension free, and only involves the p-variation of two paths and the ‘uniform’ distance between the first terms. Applications include estimation of the difference of the signatures of two uniformly close paths (Lyons and Xu, 2011 [6]), and convergence rates for Gaussian rough paths (Riedel and Xu, 2012 [7]). [Copyright &y& Elsevier]

2D cell culture is widely utilized to develop anti-cancer drugs and to explore the mechanisms of cancer tumorigenesis and development. However, the findings obtained from 2D culture often fail to provide guidance for clinical tumor treatments since it cannot precisely replicate the features of real tumors. 3D tumor models capable of recapitulating native tumor microenvironments have been proved to be a promising alternative technique. Herein, we constructed a breast tumor model from novel hyaluronic acid (HA) hydrogel which was prepared through photocrosslinking of methacrylated HA. The hydrogel was used as a biomimetic extracellular matrix to incubate MCF-7 cells. It was found that methacrylation degree had great effects on hydrogel's microstructure, mechanical performances, and liquid-absorbing and degradation abilities. Optimized hydrogel exhibited highly porous morphology, high equilibrium swelling ratio, suitable mechanical properties, and hyaluronidase-responsive degradation behavior. The results demonstrated that the HA hydrogel facilitated MCF-7 cell proliferation and growth in an aggregation manner. Furthermore, 3D-cultured MCF-7 cells not only up-regulated the expression of VEGF, bFGF and interleukin-8 but exhibited greater invasion and tumorigenesis capabilities compared with 2D-cultured cells. Therefore, the HA hydrogel is a reliable substitute for tumor model construction. [Display omitted] • The hyaluronic acid hydrogel was synthesized by a facile photo-crosslinking approach. • 3D breast tumor models were successfully constructed from hyaluronic acid hydrogels. • 3D-cultured MCF-7 cells efficiently replicated key cellular features of tumor in vivo. • 3D-cultured MCF-7 cells exhibited enhanced tumorigenicity than 2D-cultured ones. [ABSTRACT FROM AUTHOR]

Immunotherapy shows great promise in the treatment of hepatocellular carcinoma (HCC), however, the low response rate of HCC patients to immunotherapy caused by inadequately immunogenic and immunosuppressive tumor microenvironment (TME) is a huge challenge. Herein, a donut‐like multifunctional polysaccharide nanoplatform (GH‐PID) is constructed from doxorubicin/aldehyde hyaluronan nanoring, indocyanine green/hydroxyethyl chitosan nanocomplex, and HCC‐bitargeted galactosamine‐hyaluronan conjugate via a facile self‐assembly process. The GH‐PID nanodonuts exhibit excellent HCC‐targeted ability and synergetic photochemotherapy effect with a coefficient index of about 0.44. Moreover, near infrared laser‐irradiated GH‐PID nanodonuts show robust therapeutic efficacy in HCC mouse models by virtue of photochemotherapy‐augmented immunogenic cell death (ICD) effect. The remarkable ICD in combination with programmed death‐1 antibody efficiently eradicates primary tumors and inhibits distant tumor growth and lung metastasis of HCC by maturing dendritic cells, increasing CD8+ T cell infiltration, suppressing the expansion and trafficking of immunosuppressive myeloid‐derived suppressor cells, and ameliorating immunosuppressive TME. This study provides a facile and versatile strategy to construct polysaccharide nanodonuts integrating multifunctionality and highly efficient HCC‐targeted ability, and the nanodonuts‐based ICD inducer holds great promise for potentiating systemic antitumor immunity and programmed death‐1/programmed death‐ligand 1 blockade efficacy. [ABSTRACT FROM AUTHOR]

To rationally assess the consequence of a ship's hull girder collapse, it is necessary to know the post-ultimate strength behavior of the hull girder including the global deformation and motions under extreme wave-induced loads. In the foregoing research, the authors proposed a numerical analysis system to predict the collapse behavior in waves including the post-ultimate strength behavior. The primary objective of the present paper is to clarify the parametric dependencies of the severity of the collapse in a rational manner. The parameters may include those related to load-carrying capacity and the extreme loads. To this end, an analytical solution to describe the post-ultimate strength behavior is derived. Assuming that a plastic hinge is formed at the midship during the collapse procedure, the whole ship is modeled as a two-rigid-bodies system connected to each other amidship via a nonlinear rotational spring, which represents the nonlinear relationship between the bending moment and the rotational angle. The relationship may be modeled as piece-wise linear curves. It is further assumed that large motions and elastic/plastic deformations of the hull girder may not affect the load evaluations, and that the hull girder is subjected to a large single wave. Some important parameters to predict the severity of the collapse are specified based on the analytical solution. [ABSTRACT FROM AUTHOR]

Purpose – The purpose of this paper is to understand the root cause of a large number of quality problems in the current Chinese construction market. Design/methodology/approach – Information economics theory is used to analyze the cause of construction quality problems related to the specific case of the Wenchuan earthquake of China. Findings – The single low price competition in the construction tender market leads to the serious adverse selection and moral hazard behavior of bidding firms. The main solution to this problem is the introduction and improvement of an independent inspection/supervision mechanism. Originality/value – The paper systematically analyzes the evaluation method of the lowest price winning bidding policy, which is the fundamental cause of adverse selection and moral hazard problems in the Chinese construction market. [ABSTRACT FROM AUTHOR]

Owing to the fluctuations in the financial markets, many financial variables such as expected return, volatility, or exchange rate may occur imprecisely. But many portfolio selection models consider precise input of these values. Therefore, this paper studies a multiobjective international asset allocation problem under fuzzy environment. In our portfolio selection model, both of the return risk and the exchange risk are considered. The coefficient matrices in the objectives and constraints and the decision value are considered as fuzzy variables. The calculation of the portfolio and efficient frontier is derived by considering the exchange risk in the fuzzy environment. An empirical study is performed based on a portfolio of six securities denominated in six different currencies, i.e., USD, EUR, JPY, CNY, HKD, and GBP. The α-level closed interval portfolio $\tilde X_\alpha$ and the fuzzy efficient frontier are obtained with different values of α ∈ (0, 1]. The empirical results indicate that the fuzzy asset selection method is a useful tool for dealing with the imprecise problem in the real world. [ABSTRACT FROM AUTHOR]

Abstract: A similarity search on the structural analogs of an inhibitor of BACE-1 with IC50 2.8μM, which contained a P1 benzothiazole group together with a triazine ring linked by a secondary amine group, was described in this Letter and some more potent inhibitors against BACE-1 were identified. The most potent compound 5 (IC50 =0.12μM) increases the inhibitory potency by 24 folds. Our results suggest that a pyrrolidinyl side group at the P3′ and P4′ of the inhibitors are favored for strong inhibition and a small aromatic group at the P4 position is also essential to the potency. [ABSTRACT FROM AUTHOR]

Abstract: Nowadays identification of novel non-peptide β-secretase (BACE-1, hereinafter) inhibitors with low cytotoxicity and good blood–brain barrier (BBB) property holds common interest of drug discovery for Alzheimer’s disease. Twenty SPECS compounds were tested in BACE-1 FRET assays and methylthiazoletetrazolium (MTT) cytotoxicity experiment. Two compounds: 2 and 15 demonstrated IC50 values of 0.53 and 9.4μM. In addition, 2 showed least toxic effect to the neuroblastoma cells. The results from both in silico and in vitro studies provided new pharmacophoric entities for chemical synthesis and optimization on the current discovered BACE-1 small molecule inhibitors. [Copyright &y& Elsevier]

Abstract: Owing to the fluctuations in the financial markets from time to time, some input variables, in particular the interest rate, spot exchange rate and volatility, in the Garman–Kohlhagen model [M.B. Garman, S.W. Kohlhagen, Foreign currency option values, Journal of International Money and Finance 2 (1983) 231–237] cannot be expected in a precise sense. Therefore, the fuzzy set theory introduced by Zadeh [L.A. Zadeh, Fuzzy sets, Information and Control 8 (1965) 338–353] can provide a useful tool to deal with this kind of impreciseness. In this paper, three different versions of the G–K model, the put-call parity relationship and the calculation formulas of the Greek letters according to these three different G–K models are then proposed based on fuzzy set theory. Under the considerations of fuzzy foreign and domestic interest rates, fuzzy spot exchange rate and fuzzy volatility, the European currency option prices and the Greek letters turn into fuzzy numbers or closed intervals. This means that the investors can pick any European currency option price and Greek letters with an acceptable belief degree or belief degree weighting parameter for his later use. The empirical results indicate that the Greeks calculated under fuzzy environment can be considered as a useful tool for managing option risk for an option writer. [Copyright &y& Elsevier]

Abstract: This Letter describes an efficient approach by integrating virtual screening with bioassay technology for finding small organic inhibitors targeting β-secretase (BACE-1). Fifteen hits with inhibitory potencies ranging from 2.8 to 118μM (IC50) against β-secretase were successfully identified. Compound 12 with IC50 of 2.8μM is the most potent hit against BACE-1. Docking simulation from gold 3.0 suggests putative binding mode of 12 in BACE-1 and potential key pharmacophore groups for further designing of non-peptide compounds as more powerful inhibitors against BACE-1. [Copyright &y& Elsevier]

Temporal dependency and mutual impact are two major aspects of the qualitative analysis of stock prices. Modeling the dynamic and complex nature of both the timeline and the mutual impact network is a challenging task for stock price prediction. Furthermore, if we want to capture the high-frequency changes of stock price, the time series will become extremely long, leading to a practical challenge in terms of modeling. To address these challenges, this paper proposes a novel memory-based hierarchical recurrent neural encoder (MHieR-encoder) to embed the time series of stock price into a new representation that preserves (i) the sequential dependency of the time series and (ii) the proximity relationships across stocks in the impact network. The hierarchical structure of the proposed model can easily capture the long-range dependence from an extremely long time series, including in terms of high-frequency prices. Moreover, to capture the dynamic mutual impact across stocks, the intermediate results of the impact network will be stored in the memory module to support further exploration at the training stage. The method is validated using an extremely long time series composed of the one-minute prices derived from the all the Chinese stocks. The results show that MHieR-encoder outperforms all the 8 baselines in the bull market, bear market, calm bull market and calm bear market, and significantly improves the accuracy to 52.2% in a three-class prediction: rising, falling and flat. [ABSTRACT FROM AUTHOR]

As an emerging cancer treatment strategy, reactive oxygen species-based tumor catalytic therapies face enormous challenges due to hypoxia and the overexpression of glutathione (GSH) in the tumor microenvironment. Herein, a self-assembled copper-based nanoplatform, TCCHA, was designed for enzyme-like catalysis-enhanced chemodynamic/photodynamic/antiangiogenic tritherapy against hepatocellular carcinoma. TCCHA was fabricated from Cu2+, 3,3′-dithiobis (propionohydrazide), and photosensitizer chlorine e6 via a facile one-pot self-assembly strategy, after which an aldehyde hyaluronic acid was coated, followed by loading of the antivascular drug AL3818. The obtained TCCHA nanoparticles exhibited pH/GSH dual-responsive drug release behaviors and multienzymatic activities, including Fenton, glutathione peroxidase-, and catalase-like activities. TCCHA, a redox homeostasis disruptor, promotes ⋅OH generation and GSH depletion, thus increasing the efficacy of chemodynamic therapy. TCCHA, which has catalase-like activity, can also reinforce the efficacy of photodynamic therapy by amplifying O2 production. In vivo, TCCHA efficiently inhibited tumor angiogenesis and suppressed tumor growth without apparent systemic toxicity. Overall, this study presents a facile strategy for the preparation of multienzyme-like nanoparticles, and TCCHA nanoparticles display great potential for enzyme catalysis-enhanced chemodynamic/photodynamic/antiangiogenic triple therapy against cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] Copper-based nanomaterials show considerable potential in the chemodynamic therapy of cancers. However, their clinical application is restricted by low catalytic activity in tumor microenvironment and copper-induced tumor angiogenesis. Herein, a novel copper-doxorubicin-anlotinib (CDA) nanoconjugate was constructed by the combination of copper-hydrazide coordination, hydrazone linkage and Schiff base bond. The CDA nanoconjugate consists of a copper-3,3′-dithiobis(propionohydrazide)-doxorubicin core and an anlotinib-hyaluronan shell. Benefiting from hyaluronan camouflage and abundant disulfide bonds and Cu2+, the CDA nanoconjugate possessed excellent tumor-targeting and glutathione-depleting abilities and enhanced chemodynamic efficacy. Released doxorubicin significantly improved copper-mediated chemodynamic therapy by upregulating nicotinamide adenine dinucleotide phosphate oxidase 4 expression to increase intracellular H 2 O 2 level. Furthermore, the nanoconjugate produced excessive •OH to induce lipid peroxidation and mitochondrial dysfunction, thus greatly elevating doxorubicin-mediated chemotherapy. Importantly, anlotinib effectively inhibited the angiogenic potential of copper ions. In a word, the CDA nanoconjugate is successfully constructed by combined coordination and pH-responsive linkages, and displays the great potential of copper-drug conjugate for targeted synergistic chemo/chemodynamic/antiangiogenic triple therapy against cancers. [ABSTRACT FROM AUTHOR]

The inertness of carbon felt as cathode is still one of the challenges encountered in the degradation of pollutants by electro-Fenton. In this study, we used a simple ultrasonic oxidation method to introduce oxygen-containing groups and defect carbons on carbon felt surface to improve the electro-Fenton performance. The modified carbon felts were prepared by ultrasonic treatment in three dilute solutions of HNO3, H2SO4, and HNO3–H2SO4. Ultrasound can provide an extra energetic environment to accelerate the oxidation process, while NO3− has stronger oxidation properties in the presence of excess H+, greatly increasing the amounts of C–O–C/C=O and C–C active sites on carbon felt surface. And an electro-Fenton system with modified CF as the cathode was used to degrade rhodamine B, and the factors affecting the degradation were discussed. The results showed that the modified cathode material was significantly more efficient in degrading rhodamine B, under the conditions of O2 flow rate of 0.3 L min−1, pH = 3, voltage of − 0.7 V, and addition of 0.2-mM Fe2+, HNO3–H2SO4 solution modified CF with 37% higher than that of the raw CF, and the decolorization rate reached 96% after 120 min. Modified carbon felt still has good degradation properties after 5 cycles. The CF was modified by ultrasonic oxidation technique to introduce oxygen-containing functional groups and C-sp3 on the surface of the carbon felt.Using this CF as a cathode for the degradation of RhB in an electro-Fenton system. [ABSTRACT FROM AUTHOR]

Combination of different therapy modalities with multiple tumoricidal mechanisms has emerged as a promising anticancer strategy. Herein, we reported an aldehyde/catechol-functionalized hyaluronic acid (DAHA) and hydroxyethyl chitosan (HECS) decorated gold nanorod (GNR) platform for combined chemo-photothermal therapy of breast cancer. The DAHA was synthesized by conjugating dopamine onto oxidized hyaluronic acid. The nanoplatform was prepared by successively modifying GNR with DAHA via Au-catechol bonds, conjugating DOX onto DAHA moiety through Schiff base linkage, and coating HECS interlayer for charge-reversal and hyaluronic acid corona for tumor cell targeting. The resulting nanoplatform GNR-HADOXCH exhibited acid-triggered surface charge-reversal and pH/NIR dual-responsive drug release behaviors. The nanoplatform could be efficiently internalized into MCF-7 breast cancer cells and displayed greater cancer cell killing than individual modalities. Therefore, polysaccharide decoration could ensure the co-delivery of GNR and DOX into cancer cells, and the developed GNR-HADOXCH holds great potential for breast cancer treatment. Unlabelled Image • The versatile nanoplatform was prepared via a facile and effective self-assembly method. • The nanoplatform exhibited acid-triggered surface charge-reversal property. • The nanoplatform had pH/NIR dual-responsive drug release behavior. • Receptor recognition and charge-reversal dual-enhanced cellular internalization. • MCF-7 cells could be efficiently killed by combined chemo-photothermal therapy. [ABSTRACT FROM AUTHOR]

Background: Acute paraquat poisoning-induced multiple organ dysfunction syndrome (MODS) leads to the high mortality. This study aimed to investigate the clinical significance of microRNA-200b-3p (miR-200b-3p), an upstream inhibitor of high-mobility group box 1 (HMGB1), in acute paraquat poisoning patients for the prediction of MODS and survival. Methods: This study enrolled 80 patients with MODS induced by paraquat and 94 healthy volunteers. The interaction between miR-200b-3p and HMGB1 was identified by luciferase reporter assay. miR-200b-3p levels were measured by quantitative real-time (QRT) PCR. High-mobility group box 1 levels were measured by enzyme-linked immune sorbent assay (ELISA). Receiver operating characteristic analysis was used to evaluate the diagnostic value of miR-200b-3p in screening MODS patients. The relationship between miR-200b-3p and the 28-day survival of MODS patients was evaluated by Kaplan–Meier curves and log-rank test. Cox regression analysis was used to assess the prognostic value of miR-200b-3p. Correlation between miR-200b-3p and HMGB1 was confirmed by Pearson's correlation analysis. Results: miR-200b-3p directly target HMGB1. miR-200b-3p, decreased in MODS patients, had high diagnostic value to screen MODS patients from healthy controls. Additionally, serum miR-200b-3p was decreased in non-survivors, and patients with low miR-200b-3p level had poor 28-day survival. Serum miR-200b-3p could independently predict the survival prognosis. Moreover, serum HMGB1 level was increased in MODS patients, and was negatively correlated with miR-200b-3p level. Conclusion: Decreased miR-200b-3p may function as a biomarker for the diagnosis and survival prognosis of MODS patients, and miR-200b-3p may be involved in the progression of acute paraquat-induced MODS via regulating inflammatory responses by targeting HMGB1. [ABSTRACT FROM AUTHOR]

• Multifunctional PEG-b-polypeptide-decorated gold nanorod nanoplatform was developed. • DOX was conjugated onto the nanoplatform via pH-sensitive hydrazone linkage. • Release behavior of DOX from the nanoplatform was reduction/pH dual-responsive. • Combined photothermal chemotherapy achieved great anti-cancer efficacy in MCF-7 cells. The combination of chemotherapy and photothermal therapy is acknowledged as one of the most promising approaches in cancer treatment. Targeted delivery and controlled drug release are two important factors for combined chemo-photothermal therapy. In this study, a multifunctional nanoplatform based on gold nanorod (GNR) decorated with folate-conjugated poly(ethylene glycol)- b -poly(L-γ-glutamylhydrazine) (FEGGH) containing disulfide linker and dihydroxyphenyl groups was developed for targeted combined chemo-photothermal therapy of breast cancer. FEGGH was synthesized by ring-opening polymerization of γ-benzyl- l -glutamate -N- carboxyanhydride using folate/cystamine-heterobifunctionalized poly(ethylene glycol) as an initiator, following by hydrazinolysis and carbodiimide reactions. FEGGH was decorated onto GNR through Au-catechol bonds. Chemotherapeutic drug doxorubicin (DOX) was loaded onto the nanoplatform through pH-sensitive hydrazone linkage, obtaining final product FEGGHDOX-GNR. The DOX-loaded nanoplatform displayed excellent photostability and reduction/pH dual-responsive drug release behavior. Cytological studies demonstrated the effective internalization of FEGGHDOX-GNR into MCF-7 cells via folate-mediated endocytosis and additive therapeutic effect of combined photothermal-chemotherapy. These results indicate that our nanoplatform may be a promising strategy for targeted combined chemo-photothermal therapy of breast cancer. [ABSTRACT FROM AUTHOR]

This study examines the asymmetric volatility spillover effect using realized measures across 22 international stock markets. The findings suggest a high connectedness among global equity markets, with downside risk spillover significantly higher than upside risk spillover over time. Besides, Europe has a higher connectedness than the American and Asia-Pacific markets, and risk contagion is from the European and American developed markets to the Asia-Pacific regions. The study further identifies implied volatility index and market liquidity as the main positive determinants of risk spillover, which are robust across different rolling window lengths and horizons. We also find that the explanatory power is more significant during financial crises. • High-frequency data is used to analyze global asymmetric volatility spillover effects. • Over time, downside risk spillover surpasses upside risk spillover significantly. • Risk contagion is from the developed markets to the Asia-pacific regions. • Developed markets connected better than emerging markets. • VIX and market liquidity in risk-transmitting markets drive volatility spillover. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • AHA-decorated bifunctionalized HECS-GNR conjugate was developed. • DOX was loaded onto the conjugate via hydrazone linkage. • The conjugate displayed pH-responsive surface charge reversal and drug release. • The conjugate exhibited synergetic photothermal chemotherapy of breast cancer cells. Abstract Chemo-photothermal combination therapy is a promising strategy for cancer treatment. In this study, to achieve the combined photothermal-chemotherapy of breast cancer, a pH-sensitive oxidized hyaluronic acid-decorated dihydroxyphenyl/hydrazide bifunctionalized hydroxyethyl chitosan (DHHC)-gold nanorod (GNR) conjugate was developed. DHHC was synthesized by successive dihydroxyphenylation and hydrazidation of hydroxyethyl chitosan through carbodiimide reaction and click chemistry, respectively. The conjugate was obtained by chemically bonding DHHC onto GNR via Au-catechol bonds. Doxorubicin (DOX) was loaded onto the conjugate via an acid-labile hydrazone linkage with a drug loading content of 5.1%. DOX-loaded conjugate displayed good stability in neutral aqueous solutions and exhibited pH-responsive drug release and surface charge reversal behaviors. In vitro biological studies indicated that the conjugate could be effectively internalized by breast cancer MCF-7 cells and synergistic therapeutic effects were demonstrated, suggesting its great potential in combined photothermal-chemotherapy of breast cancer. [ABSTRACT FROM AUTHOR]